Methamphetamine inhibits β-chemokines and co-stimulatory molecule expression by dendritic cells

Madhavan P N Nair, Jose W. Rodriguez, Irina M. Borodowsky, Supriya Mahajan, Narayanan Nair, Tolu T. Dada, Alain Diaz-Gonzalez, Paul Katz

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

The US is currently experiencing a serious epidemic of methamphetamine (Meth) use entangled with HIV-1 infection. Blood monocyte derived dendritic cells (DC) are the first line of defense against HIV-1 infection and are the initial target of HIV-1 in injection drug users. Chemokines are known to be HIV-1 suppressing molecules and are positively associated with non- progression of HIV disease. Co-stimulatory molecules are necessary for DC maturation, effective antigen presentation, cell migration, and T cell proliferation. Although previous studies suggest that Meth deregulates various immune responses, the role of Meth on gene expression and production of β-chemokines and co-stimulatory molecules by DC has not been studied. We hypothesize that Meth induced immune defects may be mediated by dysregulation of β-chemokines (MIP-1α/CCL3, MIP-1β/CCL4 and RANTES/CCL5), co-stimulatory and maturation molecules (CD83 and CCR7) by DC. Our results show that Meth significantly downregulates the gene expression and production of β-chemokines and co stimulatory molecule by DC from normal subjects. In HIV-1 infected subjects, RANTES variant In1.1c that has been associated with accelerated HIV-1 disease progression was significantly higher compared to normal controls. Further, Meth significantly inhibited total RANTES gene expression with a reciprocal upregulation of RANTES variant In1.1c in a dose dependent manner by both immature DC (IDC) and mature DC (MDC) from normal subjects. These studies report for the first time that Meth deregulates β-chemokines and co-stimulatory molecule expression by DC. The results emanating from these studies may help to support the therapeutic application of chemokines to restore anti-HIV-1 immune responses to prevent or control HIV-1 infection in meth using populations.

Original languageEnglish
Pages (from-to)217-224
Number of pages8
JournalAmerican Journal of Infectious Diseases
Volume3
Issue number4
StatePublished - Dec 1 2007
Externally publishedYes

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Keywords

  • DC-SIGN, dendritic cell (DC) specific C type ICAM-3 grabbing nonintegrin, RANTES
  • IDC immature DC
  • MDC, mature DC
  • Regulated upon activation T-cell expressed and secreted

ASJC Scopus subject areas

  • Infectious Diseases

Cite this

Nair, M. P. N., Rodriguez, J. W., Borodowsky, I. M., Mahajan, S., Nair, N., Dada, T. T., Diaz-Gonzalez, A., & Katz, P. (2007). Methamphetamine inhibits β-chemokines and co-stimulatory molecule expression by dendritic cells. American Journal of Infectious Diseases, 3(4), 217-224.